Pilot Study of Oxaliplatin in Combination With Capecitabine in Adult Cancer Patients

OBJECTIVES:

• Determine the maximum tolerated dose (MTD) of capecitabine when administered with oxaliplatin in patients with colorectal, appendiceal, or small bowel cancer.
• Determine the clinical toxic effects associated with this regimen in these patients.
• Characterize the molecular profile of tumor tissue obtained prior to study entry for determinants of sensitivity to this regimen in this patient population.
• Characterize the molecular profile of a surrogate normal tissue (bone marrow aspirate) obtained prior to treatment and assess any potential drug-associated induction of DNA damage and inhibition of thymidylate synthase with a repeat bone marrow aspirate during therapy.
• Assess any clinical activity of this regimen in this patient population.

OUTLINE: This is a dose-escalation study of capecitabine.

Patients receive oxaliplatin IV over 2 hours on day 1 followed by oral capecitabine twice daily on days 1-5 and 8-12. Courses repeat every 3 weeks in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating doses of capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.